A natural cell-penetrating nanopeptide combined with pentavalent antimonial as experimental therapy against cutaneous leishmaniasis.

Abstract

The inadequacy of available treatments for leishmaniasis has presented up to 40% therapeutic failure. This fact suggests an urgency in the discovery of new drugs or alternative approaches for treating this disease. The objective of this study was to evaluate the antileishmanial activity of combined therapy between crotamine (CTA) from Crotalus durissus terrificus and the pentavalent antimonial Glucantime® (GLU). The assays were in vitro performed measuring the inhibition of Leishmania amazonensis amastigotes, followed by the evaluation of cellular production of cytokines and nitrites. After that, analytical methods were performed in order to characterize the molecules involved in the study by Mass Spectrometry, molecular affinity through an in silico assay and Surface Plasmon Resonance. In vivo experiments with BALB/c mice were performed by analyzing parasitemia, lesion size and immunological mediators. In the in vitro experiments, the pharmacological association improved the inhibition of the amastigotes, modulated the production of cytokines and nitric oxide. The therapy improved the effectiveness of the GLU, demonstrating a decreased parasitemia in the infected tissues. Altogether, the results suggest that the combined approach with CTA and GLU may be a promising alternative for the treatment of cutaneous leishmaniasis.

• Authors: João Rafael Valentim Silva, Neuza Biguinati de Barros, Sharon Rose Aragão Macedo, Amália Dos Santos Ferreira, Leandro Soares Moreira Dill, Fernando Berton Zanchi, Johnny Ramos do Nascimento, Flávia Raquel Fernandes do Nascimento, Marcos Roberto Lourenzoni, Leonardo de Azevedo Calderon, Andreimar Martins Soares, Roberto Nicolete
• Journal: Experimental parasitology (Exp Parasitol) Vol. 217 Pg. 107934 (Oct 2020) ISSN: 1090-2449 [Electronic] United States
• PMID: 32698075 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Antiprotozoal Agents
• Crotalid Venoms
• Drug Combinations
• Nitrites
• Tumor Necrosis Factor-alpha
• Interleukin-12
• Nitric Oxide
• Meglumine Antimoniate
• crotamine

Topics

• Animals
• Antiprotozoal Agents (pharmacology, therapeutic use)
• Crotalid Venoms (pharmacology, therapeutic use)
• Crotalus
• Drug Combinations
• Interleukin-12 (blood, metabolism)
• Leishmania mexicana (drug effects, isolation & purification)
• Leishmaniasis, Cutaneous (drug therapy)
• Lymph Nodes (parasitology)
• Macrophages, Peritoneal
• Mass Spectrometry
• Meglumine Antimoniate (pharmacology, therapeutic use)
• Mice
• Mice, Inbred BALB C
• Molecular Docking Simulation
• Nitric Oxide (metabolism)
• Nitrites (analysis)
• Tumor Necrosis Factor-alpha (blood, metabolism)